The present invention relates to a convenient strip test device capable Qf running several color tests simultaneously using a sample such as serum, plasma, or whole blood and a device capable of detecting and measuring the results simultaneously, thereby, providing the measurement of specific damage to organs due to certain diseases with one on-site simple testing method. This provides rapid communication of results to a site remote from the patient by electronic communication.
Medically, it is a great advantage as part of a preventive approach to serious organ or metabolic dysfunction to diagnose the disease or dysfunction early. This health alert can be only accomplished by having a convenient system, which allows frequent testing of analytes associated with disorders or dysfunction of major organs to provide early diagnosis. The preferred testing should provide immediate answers at the patient""s site, such as at the physician""s office, home by health care professionals, or by self testing, and/or long term care facilities so that serious consequences can be avoided or minimized. For such diagnostic testing, the sample of choice is blood.
In the past, several calorimetric methods have been used in the determination of analytes. The Seralyzer(copyright) (Ames division of Miles Labs or Bayer) and Ektachem(copyright) (Eastman Kodak) system provide quantitation for the determination of several analytes. However, these systems use serum as a sample, not blood. In these cases, the separation of serum from blood requires centrifugation in a laboratory, which generally cannot be performed at the patient""s site. Additionally, the analyzers are large in size and the measurements are not done simultaneously but one at a time.
Similarly the dry-chemistry tests provided by Kyoto Daiichi Kagaku for different analytes, also use serum as a sample. Other early inventions involved the measurement of analytes in serum or plasma, not whole blood, such as U.S. Pat. Nos. 5,798,272 and 5,589,399.
Other inventions related to detection of analytes are described in U.S. Pat. Nos. 4,323,536; 5,126,276, and 5,656,503.
Systems known in the prior art that measure analytes in blood are i-Stat(copyright) (I-Stat Inc.) and Reflotron(copyright) (Boehringer Mannheim). However, the i-Stat system uses an electrochemical methodology, as opposed to calorimetric. The Reflotron is a rather large and complex analyzer, which provides the test answers one at a time and does not measure several analytes simultaneously.
Another system that measures analyte in whole blood is the Stat-Site(copyright) (GDS Technology), disclosed in U.S. Pat. No. 5,104,619. This system however differs from the present invention in the complexity of the device, the system lacks the ability to measure several analytes simultaneously providing the results one test at a time, and the sample application area is very small, making application of the sample difficult and giving potentially inaccurate results if the sample has air bubbles.
U.S. Pat. No. 5,110,724 (Cholestech Corp.) is another system that measures analytes in whole blood. However, the system has several drawbacks for use as a point-of-care diagnostic device. These are, the system is not portable; it has a common light source, therefore, it can only measure one color which limits the type of analytes it can measure; the area for sample application and transport zone is complex, leading to a central blood filtering mechanism which separates plasma or serum from blood with the disadvantage of becoming clogged particularly with a high hematocrit sample. In addition, the blood sample application area is very small making it difficult and inconvenient for sample application and resulting in possibly aborting the test when air bubbles are present.
It is an object of the present invention to overcome the aforesaid deficiencies in the prior art.
It is another object of the present invention to provide a test strip which can be used with whole blood, serum, or plasma.
It is another object of the present invention to provide a simple, easy to use device to test several analytes simultaneously at the site of the patient so that results can be communicated by electronic means to a remote health care site.
It is a further object of the present invention to provide a convenient device in which placing or application of blood samples from venous or capillary blood, such as from a finger stick or a heel stick is convenient and user friendly, whether the application is direct or with a transferring dropper or device.
It is another object of the present invention to provide a device in which the individual reagent pads for each analyte have optional individual filtering areas, as opposed to a central filtering area, so as to minimize the possibility of clogging when whole blood is analyzed.
It is yet another object of the present invention to provide a reflectance meter that provides an individual light source for each reagent pad, providing an optimal method to detect the color reaction necessary for determining each analyte.
The present invention, surprisingly, overcomes all of the difficulties mentioned above by using a sample distributing layer placed uniformly over the pads to allow convenient sample application and uniform distribution of sample for each and all of the individual test pads. Where whole blood is the sample, a filter is placed uniformly over the pads to ensure that the blood is uniformly filtered. The present invention includes a system for measuring the color change in the reagent pads preferably by use of a hand-held portable meter capable of measuring different wave lengths for each pad, thereby increasing its utility to measure a variety of analytes simultaneously.
The device provides the concentration of analytes in whole blood or other sample by calorimetric methods with ease of sample application. The system consists of a strip type structure and a hand held meter that measures the reflectance of several analytes simultaneously. The system is simple and allows for convenient sample application. The method provides a quick and easy simultaneous measurement of several specific disease related analytes and makes possible frequent checks on overall body functions and immediate communication of such functions by electronic means.
For example, increase in concentration of creatinine and BUN (blood urea nitrogen) in blood serves as a marker of kidney dysfunction, increase in alanine aminotransferase enzyme (ALT) in blood serves as a marker of liver dysfunction, increase or decrease in glucose concentration in blood serves as a marker of pancreatic dysfunction i.e. diabetes, increase in cholesterol level serves as a marker of cardiovascular dysfunction, bilirubin serves as a marker for liver dysfunction, etc. The invention can also be used for on-site required testing of neonates for PKU, galactosemia, T4, etc., which today require sample transfer to remote locations for analysis.
The test strip is constructed (see FIG. 2 and FIG. 3), so that the uppermost surface or layer, which is physical or chemical in nature, to which the sample is applied, distributes the sample uniformly and quickly over the length of the strip, such as polyester filtration media by Reemay or Nylon Mesh. The second surface of the device is an optional blood-filtering layer, (see FIG. 2 and FIG. 3) such as a glass fiber matrix that, due to its porosity, allows the serum or plasma to go through while retaining the particulate blood cells. The filtering matrix or layer, when used, extends over all the reagent pads.
Both these matrices are adhered to the bottom structure, the fourth surface, at both ends, through an adhering area such as double sticking tape. In an alternative configuration, an impermeable top layer with a rectangular opening over all the reagent pads can serve to hold together all the layers, the fifth surface, as shown in FIG. 4 and FIG. 5, by adhering to the bottom (support) layer.
The third surface of the device is composed of individual reagent pads made of bibulous material, such as Whatman 54 type matrices, or other membrane such as polyethylene sulfone that absorb the serum or plasma that gets through the filtering layer. Each individual reagent pad may be composed of one or more layers (FIG. 2 and FIG. 3 show two reagent layers) each containing the chemicals necessary for producing the color reactions of the different blood analytes to be tested. The reagent pads are adhered to the support structure or fourth surface.
The fifth surface, shown in FIG. 4 and FIG. 5, is a support structure, which has a longitudinal aperture over all the reagent pads. This support structure does not interfere in the convenience of sample application of the device. Therefore, using both devices the method is the same consisting of applying the sample anywhere on the diffusion or distribution layer, optional separation of red blood cells in the filtering layer, and letting the serum or plasma pass through the reagent area. Furthermore, when the serum or plasma reacts with the chemicals of the reagent pads, the color is produced and is read through apertures in the bottom structure with any color measuring device, including the eye.
The color measuring device may comprise one light source with several different filters, or a plurality of light sources and appropriate light detectors. The color measuring device may be a reflectance meter with a plurality of light emitting diodes (LED""s) as light sources with a detector for each light source.